UNIT III_Amino acid Metabolism biochemistry

UNIT III_Amino acid Metabolism.pptx

1. UNIT: III Amino acid metabolism By Mrs. Sonali Nikam Assistant professor Faulty of Pharmaceutical Sciences

2. Content General reactions of amino acid metabolism: Transamination, deamination & decarboxylation, urea cycle and its disorders Catabolism of phenylalanine and tyrosine and their metabolic disorders (Phenyketonuria, Albinism, alkeptonuria, tyrosinemia) Synthesis and significance of biological substances; 5-HT, melatonin, dopamine, noradrenaline, adrenaline Catabolism of heme; hyperbilirubinemia and jaundice

3. Catabolism of phenylalanine and tyrosine Phenylalanine and tyrosine are aromatic amino acids. Phenylalanine is an essential amino acid while tyrosine is non-essential Predominant metabolism of phenylalanine occurs through tyrosine. Tyrosine is incorporated into proteins and is involved in the Synthesis of a variety of biologically important compounds - epinephrine, norepinephrine, dopamine (catecholamines), thyroid hormones and the pigment melanin

4. The only function of Phenylalanine is its conversion to tyrosine. For this reason, ingestion of tyrosine can reduce the dietary requirement of phenylalanine this Phenomenon is referred to as 'sparing action’ of tyrosine on phenylalanine . Due to a defect in phenylalanine hydroxylase, the conversion of phenylalanine to tyrosine is blocked resulting in the disorder phenylketonuria (PKU).

5. Conversion of phenylalanine to tyrosine Phenylalanine is hydroxylated at para-position by phenylalanine hydroxylase to produce tyrosine (p-hydroxy phenylalanine). Irreversible reaction. Requires specific coenzyme biopterin . Enzyme phenylalanine hydroxylase is present in the liver . Reaction involves the incorporation of one atom of molecular Oxygen (O2) into the para position of phenylalanine

6. Degradation of Tyrosine (phenylalanine) The metabolism of phenylalanine and tyrosine is considered together the sequence of reactions occurs.

7. Transamination Decarboxylation awa hydroxylation Cleave benzene ring Isomerization Hydrolysis

8. Synthesis and significance of biological substances; Melatonin Melanin (Creek: melan -black) is the pigment of skin, hair and eye. The synthesis of melanin occurs in melanosomes present in melanocytes, the pigment-producing cells. Melanin-the colour pigment : The skin colour of the individual is determined by the relative concentrations of black and red m elanins. This in turn, is dependent on many factors, both genetic and environmental.

9. The presence of moles on the body represents a localized severe hyperpigmentation due to hyperactivity of melanocytes. On the other hand, localized absence or degeneration of melanocytes results in white patches on the skin commonly known as leukoderma . Albinism is an inborn error with generalized lack of melanin synthesis . Albinism (Greek: albino-white) is an inborn Error due to the lack of synthesis of the pigment melanin. lt is an autosomal recessive disorder with a frequency of 1 in 20,000.

10. Many possible causes of albinism have been identified 1. Deficiency or lack of the enzyme tyrosinase. 2. Decrease in melanosomes of melanocytes. 3. impairment in melanin polymerization. 4. Lack of protein matrix in melanosomes. 5. Limitation of substrate (tyrosine) availability. 6. Presence of inhibitors of tyrosinase.

11. T yrosinemia : Richner- Hanhart syndrome. due to a defect in the enzyme tyrosine transaminase. The result is a blockade in the routine degradative pathway of tyrosine. Accumulation and excretion of tyrosine and its metabolites-namely p-hydroxyphenylpyruvate, p- hydroxyphenyllactate, phydroxyphenylacetate, N acetyltyrosine -and tyramine are observed, Characterized by skin (dermatitis) and eye lesions and, rarely, mental retardation A. Disturbed self-coordination is seen in these patients. Neonatal tyrosinemia Absence of the enzyme p-hydroxyphenylpyruvate dioxygenase.

12. Clinical manifestations : The most important function of melanin is the protection of the body from sun radiation. Lack of melanin in albinos makes them sensitive to sunlight. Increased susceptibility to skin cancer (carcinoma) is observed. Photophobia (intolerance to light) is associated with lack of pigment in the eyes.

13. Synthesis and significance of biological substances; Catecholamines C atechol refers to the dihydroxylated phenyl ring and the amine derivatives from catechol are called catecholamine. Tyrosine is the precursor for the synthesis of catecholamines, namely dopamine, norepinephrine (noradrenaline) and epinephrine (adrenaline). Occurs in adrenal medulla and central nervous. Dopamine is predominantly synthesized in substantia nigra and coeruleus of brain. C atechol

14. Hydroxylation Rate limiting step coenzyme Decarboxylation PLP dependant Hydroxylation Methylation

15. Hyperbilirubinemia Hyperbilirubinemia is a condition in which there is a build up of bilirubin in the blood, causing yellow discoloration of the eyes and skin, called jaundice.  Hyperbilirubinemia is another term for jaundice. Bilirubin  is a molecule formed from the breakdown of heme, the iron-containing, nonprotein component of hemoglobin. Normal levels of  bilirubin  for older children and adults range from 0.3 to 1.0 mg/dL. Clinically, elevated  serum bilirubin  levels manifest as jaundice, a yellowing of the skin, sclera, and mucous membranes. Jaundice is typically visible when the total serum bilirubin (TSB) is greater than 5 mg/dL

16. What causes hyperbilirubinemia? During pregnancy, the placenta excretes bilirubin . When baby is born, baby’s liver must take over this function. There are several causes of hyperbilirubinemia and jaundice, including: physiologic jaundice : occurs as a “normal” response to your baby’s limited ability to excrete bilirubin in the first days of life breast milk jaundice : about 2 percent of breastfed babies develop jaundice after the first week breastfeeding jaundice:  occurs in some baby’s in the first week due to low intake or dehydration jaundice from hemolysis : a condition that results from the breakdown of red blood cells due to  hemolytic disease of the newborn  (Rh disease),  polycythemia , or hemorrhage inadequate liver function : due to infection or other factors

17. Who is affected by hyperbilirubinemia? About 60 percent of term newborns and 80 percent of  premature babies  develop jaundice. Infants of  diabetic  mothers and of mothers with Rh disease are more likely to develop hyperbilirubinemia and jaundice. Why is hyperbilirubinemia a concern? Although low levels of bilirubin are not usually a concern, large amounts can circulate to tissues in the brain and may cause  seizures  and brain damage. This is a condition called kernicterus. What are the symptoms of hyperbilirubinemia? Symptoms may include: yellow coloring of your baby’s skin (usually beginning on the face and moving down the body) poor feeding or lethargy